GlaxoKlineSmith plans to remove zinc from certain Super Poligrip products, The New York Times reports. The product lines include Super Poligrip Original, Super Poligrip Ultrafresh, and Super Poligrip Extra Care. An estimated 3.5 million households use these products yearly. Glaxo will continue to sell its Super Poligrip Free, which doesn't contain zinc. This comes at a troubling time for the UK-based pharmaceutical giant. Glaxo's Avandia is under heavy scrutiny for its link to heart-attack deaths. Also, on February 18th the FDA issued new guidance measures urging physicians to switch asthma patients away from medicines like Glaxo's Advair because of the possibility that the asthma medication actually worsens asthma conditions long-term. Investors are even starting to take notice of Glaxo's mounting problems with patient safety, with its stock sliding despite a $2.6 billion dollar profit last quarter alone.

The voluntary recall comes after a University of Texas research study in 2008 found that users of denture cream with zinc had excess levels of zinc in their blood. A high zinc concentration in a person's blood over several years can lead to zinc toxicity and significant neurological problems. Interestingly, GlaxoSmithKline only began disclosing the zinc in their denture creams after the University of Texas' study was published in the medical journal Neurology, but gave no specific warnings to consumers.

Glaxo issued a statement on their website on February 18, 2019, regarding their voluntary, precautionary recall claiming that health problems only occur when consumers use more than the directed amount of denture cream. However, this statement is wholly inadequate. First, there were no appropriate, specific warnings to consumers about the possible dangers of developing zinc toxicity by using excess denture adhesives containing zinc. Second, it seems fundamental that the company would have to consider that many consumers use denture creams with zinc while taking other supplements containing zinc --- easily contributing to consumers developing above-average levels of zinc over time. There is no question that zinc is an important part of our diet. However, Glaxo's official stance that increased zinc intake stems only from consumers who misuse their product is laughable. In reality, it's the company's lack of foresight or common sense that has brought upon another major health concern over one of its consumer products.

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Avandia is a prescription drug marketed by GlaxoSmithKline (GSK). Released to the U.S. market in 1999, Avandia has been used by millions of Americans to treat Type II diabetes. It works by helping to control blood sugar levels by making the cells of the body more receptive to insulin.

In 2007, though, Dr. Steven Nissen published a meta-analysis of Avandia in The New England Journal of Medicine. His study data was alarming in that it found Avandia patients had a 43% higher risk of heart attack. Glaxo downplayed the report, saying Dr. Nissen's methods were not scientifically conclusive. Nonetheless, Dr. Nissen's report drew attention of Washington. The U.S. Senate Committee on Finance conducted an independent review to determine what Glaxo knew about Avandia before the study was published in the New England Journal of Medicine.

Significant (and shocking) findings by the Senate committee after reviewing hundreds of thousands of pages of internal GSK documents concluded:

"The totality of evidence suggests that GSK was aware of the possible cardiac risks associated with Avandia years before such evidence became public.... Based on this knowledge, GSK had a duty to sufficiently warn patients and the FDA of its concerns in a timely manner. Instead, GSK executives intimidated independent physicians, focused on strategies to minimize findings that Avandia may increase cardiovascular risk, and sought ways to downplay findings that the rival drug ACTOS (pioglitazone) might reduce cardiovascular risks."

Even though the FDA decided not to pull the drug in 2007 when it was up for review, it concluded that Avandia had caused 83,000 heart attacks between 1999 and 2007. Dr. Nissen has sent the New York Times secretly recorded conversations between himself and executives at Glaxo prior to publishing the report. In the meeting, executives promised to begin a thorough analysis of the link between Avandia and heart attack risk "within days" - and three years later, no such report has published in any journal. Dr. Nissen further believes he was trying to being pressured and persuaded not to publish his findings.

Glaxo says it's open to scientific debate, but so far it seems that Glaxo has only (1) downplayed scientific evidence finding increased risks of heart attack; (2) pressured scientists to not publish scientific data which would affect Avandia sales negatively; and (3) stressed, without scientific support, that Avandia is the safest alternative Type II diabetes medication on the market.

As this story continues to unfold in the weeks ahead, it again highlights broader issues of patient safety. A pharmaceutical company, especially one which is publically traded (Glaxo is publicly traded), has one overriding goal: profit. When disclosing safety concerns might materially impact the company's ability to profit, or dramatically decrease revenue from a particular drug, time and time again these companies choose to skew evidence and downplay side effects. They skirt, manipulate, and sometimes downright defy the law, all in the name of profit.

Glaxo is not the first pharmaceutical company to hide evidence or knowingly market dangerous drugs (anyone remember the Vioxx debacle? Or, perhaps HRT or fen-phen??). And until FDA becomes more proactive in regulating these companies and ensuring independent oversight, more unnecessarily dangerous drugs will continue to be marketed in the U.S.

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The Government Accountability Office (GAO) has compiled a report looking at the steps the FDA has been taking to improve communication between the internal offices of the FDA, in an effort to protect the public from dangerous drugs released on the U.S. market. The GAO found some FDA efforts towards this goal, including having done or planning to:

·         Improve communication between the Office of Surveillance and Epidemiology (OSE, once called Office of Drug Safety) and Office of New Drugs (OND).

·         In 2010, implement new data systems facilitating quicker access to outside data, in order to facilitate “timeliness, quality, and analysis of reports of adverse events associated with human drug use.”

·         Improve funding for private contracts to provide external data for speedier access.

But is this enough? Within the FDA, scientists in the OND are tasked with reviewing, and ultimately approving, new drug applications. These same scientists are also the ones who (generally) make the determination whether to pull the same drugs off the market. Meanwhile, the OSE monitors the drug’s side-effects on the market and compiles patient complaints. However, the OSE doesn’t have much say in whether the drugs should be pulled from the market. Many outsiders would point to this bureaucratic setup as improper – to have the same scientists which approved the drug also have to be the ones puts the public at risk.

Additionally, the GAO reports that both the OND and OSE are understaffed. Both offices’ employees cite the inability to meet their responsibilities. According to the GAO the OSE must double its employees in the next year in order to keep up with workload. All of this means that both the OND and OSE are understaffed and overworked; and as a result are unable to fulfill their responsibilities.

It’s important to remember that the GAO is fully independent of the FDA, the pharmaceutical industry, and trial lawyers. In fact, it’s an investigative arm of Congress, funded by taxes. There is no incentive for the GAO to fabricate or exaggerate in any direction, and their reports should be taken as truthful and honest. Knowing this makes their reports about the inadequacies of the FDA all the more alarming. While the GAO reports the FDA is going in the right direction, it still has a tremendous amount of ground to make up. And the FDA needs to do much more to distance itself from the pharmaceutical industry. And until this happens, some Americans are at risk of taking FDA-approved medications which should not be on the market.

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The American Recovery and Reinvestment Act allocated $1.1 billion dollars to coordinate research and guide investments in comparative research funded by the Act. Some critics suggest that a whole lot of money could have been saved just by looking to the FDA.

Dr. Lisa Schwartz and Dr. Steven Woloshin have co-authored a New England Journal of Medicine article titled Lost in Transmission – FDA Drug Information That Never Reaches Clinicians, in which they talk about the fallacies of the current system, and possible ways to correct it.  Primarily, on the journey from clinical trials to FDA approval to the production of a drug label, potentially vital information is lost.  For example, the FDA approved the drug Rozerem in 2005 to treat chronic insomnia, but in one phase 3 clinical trial, the drug failed to provide any benefit at all for this condition.   In fact, a memo created by the FDA’s own medical review team debated whether to even approve the drug since the insignificant benefits provided by the drug may be outweighed by its potential side effects, but Rozerem was eventually approved.  Obviously, knowing this background information would certainly appear to have an effect on a doctor’s enthusiasm to prescribe the drug, and a patient’s willingness to take the drug. Unfortunately, though, this type of important information is not placed on the FDA’s approved drug label, so none of it is clearly communicated to the public.

To its credit, the FDA has issued new guidelines about drug labeling, such as including phase 3 trial results and other effectiveness data, but this information is not mandated as it should be.  In the case of Rozerem, the effectiveness data is still absent even after the label was updated. Bottom line - more needs to be done.

The FDA is currently undergoing a pilot test of a “drug fact boxes” which would include a succinct table of effectiveness data such as reviews and labels. This would give doctors more pertinent information about drugs and also allow patients to make a more educated decision before they take a new medication. The FDA is still debating internally how to use these “drug fact boxes.”

There are other potential alternatives, but the authors concisely (and correctly) conclude, “Whatever approach the agency adopts, it needs a better way of communicating drug information to clinicians. We don’t need to wait for new comparative-effectiveness results in order to improve practice. We need to better disseminate what is already known.”

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The Government Accountability Office (GAO) has released a new report about the FDA’s lack of post-marketing oversight in a number of the drugs which it conditionally approved.

The FDA normally makes a decision to approve a drug based on clinical trials. If the clinical trials yielded favorable results, the FDA would then likely approve the drug and sales of the drug can be introduced to the U.S. market. The downside to this traditional route, though, is that the clinical trials can take years to complete, and cost the pharmaceutical company millions of dollars.   With this in mind, in 1992 the FDA instituted an optional route to approval: surrogate end-points. Surrogate end-points are the end-results yielded by a drug in a laboratory setting which tend to show positive health benefits. For example, HIV-related drugs are often approved based on its virus-lowering power, a major factor in increased survival for HIV-infected patients. A cholesterol drug could be approved to prevent heart disease, an end-point, by showing that the drug lowers cholesterol – since there is a connection between high cholesterol and heart disease. Utilizing this approval route means that manufacturers can get their drugs to the market faster and patients in need have faster access to the drug.

Unfortunately with surrogate end-point approval there are often many factors unknown, namely long-term effects of the drug’s usage. Long term clinical studies provide this information, but drugs using surrogate end-point trials are often approved so quickly that long-term effects are not known until the drug is on the market - which means that adverse effects may not be known until after the drug’s approval. As such, the FDA approves these drugs conditionally. This means that the FDA will require the manufacturer to conduct ongoing research beyond the drug’s approval, or else the drug’s approval will be revoked.

Despite all of these conditionally approved drugs requiring the conduction of post-marketing studies, the GAO found only 52% of these drugs actually have adequately completed them. 18% haven’t even started, 7% were still ongoing, and 2% were delayed. The remaining 21% were either not yet reviewed or found no longer necessary.

The GAO also noted the FDA’s inability to provide accurate record keeping of post-marketing research. Also, the GAO found that no drug approved under the surrogate-endpoint system has ever been unapproved, despite a large number of delinquent manufacturers.

This is not the first time the FDA has come under fire from the GAO. In 2006, the GAO chastised the FDA for its lack of a clear oversight process, and inability to quickly evaluate post-marketing data.  Clearly, the FDA has a responsibility to demand post-marketing studies be completed and submitted to prove a drug’s long-term safety and efficacy.

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A survey released by The Journal of the American Medical Association (JAMA) concludes that six of the top medical journals in the U.S. published a “significant number” of ghostwritten articles in recent years, reports the NY Times.  Ghostwriting in the medical profession generally means that the research or conclusions were not written by the credited author. A dangerously common practice in the medical industry is for a pharmaceutical company to pay a group of professional writers to produce papers, and then pay scientists or physicians to attach their names to these articles. Ghostwriting has been common for years, but has received harsh media attention, especially recently.   In late July, a federal judge ordered the unsealing of confidential court documents revealing that the pharmaceutical giant Wyeth orchestrated dozens of ghostwritten articles to promote their line of hormone replacement drugs.

According to the anonymous survey of 630 published medical papers, 11% of the articles in the New England Journal of Medicine were ghostwritten. Likewise, 7.9% of the articles in JAMA, 5% of the articles in The Annals of Internal Medicine, and 2% of the articles in Nature Medicine were ghostwritten. In reality, these statistics may actually be much higher, because ghostwriting is difficult to track due to its covert nature.

Many are calling for medical journals to step up enforcement of anti-ghostwriting policies. In an article written in response to the survey, PLoS Medicine editors have made a call to the industry to institute a zero tolerance policy – identifying and retracting any ghostwritten articles and banning those authors from future publications. There’s been swift congressional support too, with Senator Chuck Grassley (R – IA) telling reporters “objective research is really at the heart of public trust in medicine.” Senator Grassley has led the Congressional charge against ghostwriting in Congress, and strongly encourages medical journals to adopt strong anti-ghostwriting policies. 

Supporters of ghostwriting say that it allows articles to be released much sooner than otherwise, thus potentially getting medically sound data to the public as soon as possible. However, this data cannot, and should not, be relied upon to make medical decisions if there is a fundamental conflict of interest. The only way medical journals can protect their integrity is to take a very firm stance against ghostwriting, and institute strict policies to identify and combat it.

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Earlier this month, drug giant Pfizer agreed to pay a $2.3 billion penalty to settle claims over payment of kickbacks and illegal drug marketing and promotion that violated federal drug laws over an extensive period of time. The $2.3 billion settlement is the largest health care fine in U.S. history.  As part of the settlement, Pfizer will pay a $1.2 billion criminal fine,  a $105 criminal forfeiture, and pay another $1 billion to Medicaid, Medicare, and other federal healthcare programs.  The government said the Pfizer promoted four prescription drugs, including the pain killer Bextra, Geodon (anti-psychotic), Zyvox (an anti-biotic) and Lyrica (an anti-epileptic), as treatments for medical conditions different than those the drugs had been approved for by the FDA.

While it’s not uncommon for doctors to prescribe drugs for off-label medical conditions, drug manufacturers are strictly prohibited from marketing drugs for uses that have not been approved by the Food and Drug Administration. According to federal authorities, Pfizer encouraged its agents to wine and dine doctors in order to encourage prescribing the four drugs for off-label medical conditions. Pfizer officials even went so far as to create phony doctor requests for medical information in order to send unsolicited information to doctors about unapproved uses and dosages.

"Combating health care fraud is one of this administration's top priorities," Assistant Attorney General Thomas Perelli said in announcing the settlement. Perelli added the settlement illustrates ways the department "can help the American public at a time when budgets are tight and health care costs are rising."

The fraud and illegal conduct by Pfizer jeopardizes public health, corrupts medical decisions by health care providers, and wastes billions of government dollars.  Hopefully, this massive settlement will be a prime example of how far the government is willing to go to combat this egregious behavior and corporate greed.

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Recently disclosed court documents reveal that Wyeth, the pharmaceutical giant behind hormone replacement medications  Premarin and Prempro,has played a “major role” in 26 scientific articles published backing the medications. The articles are being criticized as over-emphasizing the benefits of hormone replacement therapy and downplaying the known risks. Wyeth solicited and paid surrogate non-medical authors to draft the articles and then paid doctors, who were “consensus builders” within the medical community, to sign off as authors in order to create the illusion of a positive general consensus among doctors that the therapy was safe and effective. And for a time, this “ghostwriting” worked. Sales of Wyeth’s HRT drugs soared to $2 billion in 2001.

But, in 2002, a huge ($700 million, 8 year) U.S. government study (WHI) stopped early when researchers found menopausal patients faced a big increased risk for invasive breast cancer, heart disease, and stroke while on HRT medication.  Multiple follow-up studies have been published including one from February of 2009 in The New England Journal of Medicine that support the conclusion that the decline in U.S. breast cancer rates is largely related to the decline in HRT use.   Sales have plummeted for HRT medication in light of recent media reports, and prescriptions are down from nearly 70 million in 2001 to less than 15 million in 2008.

Wyeth claims that the practice of hiring surrogate authors who serve as “ghostwriters” and then having doctors sign off on these favorable articles is common practice and a matter of convenience, not deception. Wyeth also claims that the articles are scientifically accurate. Even if convenience is a valid consideration – and even if the numbers in the articles were accurate – that does not mean that the articles were not written in a way favorable to Wyeth (when in fact, they were). Nor did the articles disclose Wyeth’s funding of the article’s production. Effectively – whether or not Wyeth’s ghostwritten articles were truthful in what they did say is irrelevant because it was deceptive in what they did not say.

Our firm has been deeply involved with HRT litigation, and we currently are representing over 100 women injured by HRT medication. In May of 2010, our firm has the first HRT trial scheduled in the State of Florida against Wyeth.

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